Challenges and opportunities of strain diversity in gut microbiome research

Just because two things are related does not mean they are the same. In analyzing microbiome data, we are often limited to species-level analyses, and even with the ability to resolve strains, we lack comprehensive databases and understanding of the importance of strain-level variation outside of a limited number of model organisms. The bacterial genome is highly plastic with gene gain and loss occurring at rates comparable or higher than de novo mutations. As such, the conserved portion of the genome is often a fraction of the pangenome which gives rise to significant phenotypic variation, particularly in traits which are important in host microbe interactions. In this review, we discuss the mechanisms that give rise to strain variation and methods that can be used to study it. We identify that while strain diversity can act as a major barrier in interpreting and generalizing microbiome data, it can also be a powerful tool for mechanistic research. We then highlight recent examples demonstrating the importance of strain variation in colonization, virulence, and xenobiotic metabolism. Moving past taxonomy and the species concept will be crucial for future mechanistic research to understand microbiome structure and function.